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Medicinal Chemistry Research

, Volume 23, Issue 3, pp 1378–1386 | Cite as

Synthesis and leishmanicidal activity of cinnamic acid esters: structure–activity relationship

  • Elver Otero
  • Sara M. Robledo
  • Santiago Díaz
  • Miguel Carda
  • Diana Muñoz
  • Julian Paños
  • Ivan D. Vélez
  • Wilson CardonaEmail author
Original Research

Abstract

Several cinnamic acid esters were obtained via Fischer esterification of cinnamic acids derivatives with aliphatic alcohols. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes and cytotoxic activity was evaluated against mammalian U-937 cells. The compounds 11, 1517, and 23, were active against Leishmania parasite and although toxic for mammalian cells, they still are potential candidates for antileishmanial drug development. A SAR analysis indicates that first, while smaller alkyl chains lead to higher selectivity indices (10, 11 vs. 1217); second, the degree of oxygenation is essential for activity, primarily in positions 3 and 4 (17 vs. 1820 and 22); and third, hydroxyl groups increase both activity and cytotoxicity (14 vs. 23). On the other hand, the presence of a double bond in the side chain is crucial for cytotoxicity and leishmanicidal activity (12 vs. 21). However, further studies are required to optimize the structure of the promising molecules and to validate the in vitro activity against Leishmania demonstrated here with in vivo studies.

Keywords

Leishmaniasis Antiprotozoal Caffeic acid Cinnamic acid ester 

Notes

Acknowledgments

The authors thank Dr. Javier Garcés for his help in this study. We acknowledge the support by the Universidad de Antioquia (Estrategia de Sostenibilidad 2013–2014 and CIDEPRO) and Colciencias (contract No. 357-2011).

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Elver Otero
    • 1
  • Sara M. Robledo
    • 2
    • 3
  • Santiago Díaz
    • 4
  • Miguel Carda
    • 4
  • Diana Muñoz
    • 3
  • Julian Paños
    • 4
  • Ivan D. Vélez
    • 2
    • 3
  • Wilson Cardona
    • 1
    Email author
  1. 1.Química de Plantas Colombianas, Instituto de Química, Facultad de Ciencias Exactas y NaturalesUniversidad de Antioquia (UdeA)MedellínColombia
  2. 2.Programa de Estudio y Control de Enfermedades Tropicales (PECET), Sede de Investigación Universitaria (SIU)Universidad de Antioquia (UdeA)MedellínColombia
  3. 3.CIDEPRO-Center for Development of Products against Tropical DiseasesMedellínColombia
  4. 4.Departamento de Química Inorgánica y OrgánicaUniversidad Jaume ICastellónSpain

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